In the last post, I reviewed the controlled trials on the effect of the glycemic index (GI) of carbohydrate foods on health. I concluded that there is no convincing evidence that a low GI diet is better for health than a high GI diet, and in fact the long-term trials suggest that a high GI diet may even be better for insulin sensitivity.
Despite the graphs I presented in the last post, for the "average" individual the GI of carbohydrate foods can affect the glucose and insulin response to carbohydrate foods somewhat, even in the context of an actual meal. If you compare two meals of very different GI, the low GI meal will cause less insulin secretion and cause less total blood glucose in the plasma over the course of the day (although the differences in blood glucose may not apply to all individuals).
But is that biologically significant? In other words, do those differences matter when it comes to health? I would argue probably not, and here's why: there's a difference between post-meal glucose and insulin surges and chronically elevated glucose and insulin. Chronically elevated insulin is a marker of metabolic dysfunction, while post-meal insulin surges are not (although glucose surges in excess of 140 mg/dL indicate glucose intolerance). Despite what you may hear from some sectors of the low-carbohydrate community, insulin surges do not necessarily lead to insulin resistance. Just ask a Kitavan. They get 69% of their 2,200 calories per day from high-glycemic starchy tubers and fruit (380 g carbohydrate), with not much fat to slow down digestion. Yet they have low fasting insulin, very little body fat and an undetectable incidence of diabetes, heart attack and stroke. That's despite a significant elderly population on the island.
Furthermore, in the 4-month GI intervention trial I mentioned last time, they measured something called glycated hemoglobin (HbA1c). HbA1c is a measure of the amount of blood glucose that has "stuck to" hemoglobin molecules in red blood cells. It's used to determine a person's average blood glucose concentration over the course of the past few weeks. The higher your HbA1c, the poorer your blood glucose control, the higher your likelihood of having diabetes, and the higher your cardiovascular risk. The low GI group had a statistically significant drop in their HbA1c value compared to the high GI group. But the difference was only 0.06%, a change that is biologically meaningless.
OK, let's take a step back. The goal of thinking about all this is to understand what's healthy, right? Let's take a look at how healthy cultures eat their carbohydrate foods. Cultures that rely heavily on carbohydrate generally fall into three categories: they eat cooked starchy tubers, they grind and cook their grains, or they rely on grains that become very soft when cooked. In the first category, we have Africans, South Americans, Polynesians and Melanesians (including the Kitavans). In the second, we have various Africans, Europeans (including the villagers of the Loetschental valley), Middle Easterners and South Americans. In the third category, we have Asians, Europeans (the oat-eating residents of the outer Hebrides) and South Americans (quinoa-eating Peruvians).
The pattern here is one of maximizing GI, not minimizing it. That's not because high GI foods are inherently superior, but because traditional processing techniques that maximize the digestibility of carbohydrate foods also tend to increase their GI. I believe healthy cultures around the world didn't care about the glycemic index of foods, they cared about digestibility and nutritional value.
The reason we grind grains is simple. Ground grains are digested more easily and completely (hence the higher GI). Furthermore, ground grains are more effective than intact grains at breaking down their own phytic acid when soaked, particularly if they're allowed to ferment. This further increases their nutritional value.
The human digestive system is delicate. Cows can eat whole grass seeds and digest them using their giant four-compartment stomach that acts as a fermentation tank. Humans that eat intact grains end up donating them to the waste treatment plant. We just don't have the hardware to efficiently extract the nutrients from cooked whole rye berries, unless you're willing to chew each bite 47 times. Oats, quinoa, rice, beans and certain other starchy seeds are exceptions because they're softened sufficiently by cooking.
Grain consumption and grinding implements appear simultaneously in the archaeological record. Grinding has always been used to increase the digestibility of tough grains, even before the invention of agriculture when hunter-gatherers were gathering wild grains in the fertile crescent. Some archaeologists consider grinding implements one of the diagnostic features of a grain-based culture. Carbohydrate-based cultures have always prioritized digestibility and nutritional value over GI.
Finally, I'd like to emphasize that some people don't have a good relationship with carbohydrate. Diabetics and others with glucose intolerance should be very cautious with carbohydrate foods. The best way to know how you deal with carbohydrate is to get a blood glucose meter and use it after meals. For $70 or less, you can get a cheap meter and 50 test strips that will give you a very good idea of your glucose response to typical meals (as opposed to a glucose bomb at the doctor's office). Jenny Ruhl has a tutorial that explains the process. It's also useful to pay attention to how you feel and look with different amounts of carbohydrate in your diet.
More Thoughts on the Glycemic Index
In the last post, I reviewed the controlled trials on the effect of the glycemic index (GI) of carbohydrate foods on health. I concluded that there is no convincing evidence that a low GI diet is better for health than a high GI diet, and in fact the long-term trials suggest that a high GI diet may even be better for insulin sensitivity.
Despite the graphs I presented in the last post, for the "average" individual the GI of carbohydrate foods can affect the glucose and insulin response to carbohydrate foods somewhat, even in the context of an actual meal. If you compare two meals of very different GI, the low GI meal will cause less insulin secretion and cause less total blood glucose in the plasma over the course of the day (although the differences in blood glucose may not apply to all individuals).
But is that biologically significant? In other words, do those differences matter when it comes to health? I would argue probably not, and here's why: there's a difference between post-meal glucose and insulin surges and chronically elevated glucose and insulin. Chronically elevated insulin is a marker of metabolic dysfunction, while post-meal insulin surges are not (although glucose surges in excess of 140 mg/dL indicate glucose intolerance). Despite what you may hear from some sectors of the low-carbohydrate community, insulin surges do not necessarily lead to insulin resistance. Just ask a Kitavan. They get 69% of their 2,200 calories per day from high-glycemic starchy tubers and fruit (380 g carbohydrate), with not much fat to slow down digestion. Yet they have low fasting insulin, very little body fat and an undetectable incidence of diabetes, heart attack and stroke. That's despite a significant elderly population on the island.
Furthermore, in the 4-month GI intervention trial I mentioned last time, they measured something called glycated hemoglobin (HbA1c). HbA1c is a measure of the amount of blood glucose that has "stuck to" hemoglobin molecules in red blood cells. It's used to determine a person's average blood glucose concentration over the course of the past few weeks. The higher your HbA1c, the poorer your blood glucose control, the higher your likelihood of having diabetes, and the higher your cardiovascular risk. The low GI group had a statistically significant drop in their HbA1c value compared to the high GI group. But the difference was only 0.06%, a change that is biologically meaningless.
OK, let's take a step back. The goal of thinking about all this is to understand what's healthy, right? Let's take a look at how healthy cultures eat their carbohydrate foods. Cultures that rely heavily on carbohydrate generally fall into three categories: they eat cooked starchy tubers, they grind and cook their grains, or they rely on grains that become very soft when cooked. In the first category, we have Africans, South Americans, Polynesians and Melanesians (including the Kitavans). In the second, we have various Africans, Europeans (including the villagers of the Loetschental valley), Middle Easterners and South Americans. In the third category, we have Asians, Europeans (the oat-eating residents of the outer Hebrides) and South Americans (quinoa-eating Peruvians).
The pattern here is one of maximizing GI, not minimizing it. That's not because high GI foods are inherently superior, but because traditional processing techniques that maximize the digestibility of carbohydrate foods also tend to increase their GI. I believe healthy cultures around the world didn't care about the glycemic index of foods, they cared about digestibility and nutritional value.
The reason we grind grains is simple. Ground grains are digested more easily and completely (hence the higher GI). Furthermore, ground grains are more effective than intact grains at breaking down their own phytic acid when soaked, particularly if they're allowed to ferment. This further increases their nutritional value.
The human digestive system is delicate. Cows can eat whole grass seeds and digest them using their giant four-compartment stomach that acts as a fermentation tank. Humans that eat intact grains end up donating them to the waste treatment plant. We just don't have the hardware to efficiently extract the nutrients from cooked whole rye berries, unless you're willing to chew each bite 47 times. Oats, quinoa, rice, beans and certain other starchy seeds are exceptions because they're softened sufficiently by cooking.
Grain consumption and grinding implements appear simultaneously in the archaeological record. Grinding has always been used to increase the digestibility of tough grains, even before the invention of agriculture when hunter-gatherers were gathering wild grains in the fertile crescent. Some archaeologists consider grinding implements one of the diagnostic features of a grain-based culture. Carbohydrate-based cultures have always prioritized digestibility and nutritional value over GI.
Finally, I'd like to emphasize that some people don't have a good relationship with carbohydrate. Diabetics and others with glucose intolerance should be very cautious with carbohydrate foods. The best way to know how you deal with carbohydrate is to get a blood glucose meter and use it after meals. For $70 or less, you can get a cheap meter and 50 test strips that will give you a very good idea of your glucose response to typical meals (as opposed to a glucose bomb at the doctor's office). Jenny Ruhl has a tutorial that explains the process. It's also useful to pay attention to how you feel and look with different amounts of carbohydrate in your diet.
Despite the graphs I presented in the last post, for the "average" individual the GI of carbohydrate foods can affect the glucose and insulin response to carbohydrate foods somewhat, even in the context of an actual meal. If you compare two meals of very different GI, the low GI meal will cause less insulin secretion and cause less total blood glucose in the plasma over the course of the day (although the differences in blood glucose may not apply to all individuals).
But is that biologically significant? In other words, do those differences matter when it comes to health? I would argue probably not, and here's why: there's a difference between post-meal glucose and insulin surges and chronically elevated glucose and insulin. Chronically elevated insulin is a marker of metabolic dysfunction, while post-meal insulin surges are not (although glucose surges in excess of 140 mg/dL indicate glucose intolerance). Despite what you may hear from some sectors of the low-carbohydrate community, insulin surges do not necessarily lead to insulin resistance. Just ask a Kitavan. They get 69% of their 2,200 calories per day from high-glycemic starchy tubers and fruit (380 g carbohydrate), with not much fat to slow down digestion. Yet they have low fasting insulin, very little body fat and an undetectable incidence of diabetes, heart attack and stroke. That's despite a significant elderly population on the island.
Furthermore, in the 4-month GI intervention trial I mentioned last time, they measured something called glycated hemoglobin (HbA1c). HbA1c is a measure of the amount of blood glucose that has "stuck to" hemoglobin molecules in red blood cells. It's used to determine a person's average blood glucose concentration over the course of the past few weeks. The higher your HbA1c, the poorer your blood glucose control, the higher your likelihood of having diabetes, and the higher your cardiovascular risk. The low GI group had a statistically significant drop in their HbA1c value compared to the high GI group. But the difference was only 0.06%, a change that is biologically meaningless.
OK, let's take a step back. The goal of thinking about all this is to understand what's healthy, right? Let's take a look at how healthy cultures eat their carbohydrate foods. Cultures that rely heavily on carbohydrate generally fall into three categories: they eat cooked starchy tubers, they grind and cook their grains, or they rely on grains that become very soft when cooked. In the first category, we have Africans, South Americans, Polynesians and Melanesians (including the Kitavans). In the second, we have various Africans, Europeans (including the villagers of the Loetschental valley), Middle Easterners and South Americans. In the third category, we have Asians, Europeans (the oat-eating residents of the outer Hebrides) and South Americans (quinoa-eating Peruvians).
The pattern here is one of maximizing GI, not minimizing it. That's not because high GI foods are inherently superior, but because traditional processing techniques that maximize the digestibility of carbohydrate foods also tend to increase their GI. I believe healthy cultures around the world didn't care about the glycemic index of foods, they cared about digestibility and nutritional value.
The reason we grind grains is simple. Ground grains are digested more easily and completely (hence the higher GI). Furthermore, ground grains are more effective than intact grains at breaking down their own phytic acid when soaked, particularly if they're allowed to ferment. This further increases their nutritional value.
The human digestive system is delicate. Cows can eat whole grass seeds and digest them using their giant four-compartment stomach that acts as a fermentation tank. Humans that eat intact grains end up donating them to the waste treatment plant. We just don't have the hardware to efficiently extract the nutrients from cooked whole rye berries, unless you're willing to chew each bite 47 times. Oats, quinoa, rice, beans and certain other starchy seeds are exceptions because they're softened sufficiently by cooking.
Grain consumption and grinding implements appear simultaneously in the archaeological record. Grinding has always been used to increase the digestibility of tough grains, even before the invention of agriculture when hunter-gatherers were gathering wild grains in the fertile crescent. Some archaeologists consider grinding implements one of the diagnostic features of a grain-based culture. Carbohydrate-based cultures have always prioritized digestibility and nutritional value over GI.
Finally, I'd like to emphasize that some people don't have a good relationship with carbohydrate. Diabetics and others with glucose intolerance should be very cautious with carbohydrate foods. The best way to know how you deal with carbohydrate is to get a blood glucose meter and use it after meals. For $70 or less, you can get a cheap meter and 50 test strips that will give you a very good idea of your glucose response to typical meals (as opposed to a glucose bomb at the doctor's office). Jenny Ruhl has a tutorial that explains the process. It's also useful to pay attention to how you feel and look with different amounts of carbohydrate in your diet.
JAMA Editors Try Attacking the Messenger
Early this month, yet another story surfaced about allegations of undisclosed conflicts of interest affecting the author of a highly publicized clinical trial. This story has now taken such an odd twist that it seems worth discussing in some detail. Let me first try to present some relevant facts, derived from published articles, mainly peer-reviewed, which do not seem to be in dispute, in chronological order.
2005 - In a multi-author review article on mood disorders in the medically ill, Dr Robert G Robinson, of the University of Iowa, disclosed that he served on the speakers bureau of Forest Laboratories.(1) In an article in Stroke: Clinical Updates, he made a similar disclosure.(2)
28 May, 2008 - Dr Robinson was the first author of an article published in JAMA that described a randomized controlled trial comparing placebo, problem-solving (cognitive talking) therapy, and escitalopram (Lexapro, Forest Laboratories) in the prevention of depression in patients who have had strokes.(3) Patients who received placebo had a higher rate of depression (11 major, 2 minor cases, 22.4%) than patients who received escitalopram (3, 2, 8.5%) or who received problem-solving therapy (5,2, 11.9%). At the end of the article, Dr Robinson disclosed, "over the past 5 years, Dr Robinson reports serving as a consultant to the former Hamilton Pharmaceutical Company and Avanir Pharmaceutical Company," but made no disclosure about any financial relationship with Forest. In a news article published the day before, Dr Robinson was quoted as saying, "I think every stroke patient who can tolerate an antidepressant should be given one to prevent depression," but did not advocate the use of problem solving therapy.(4)
15 October, 2008 - In a letter to JAMA, Lacasse and Leo asked whether Robinson et al had done an analysis directly comparing problem-solving therapy and escitalopram, and noted that the reported incidence data for stroke in the two treatment groups suggest that the difference in treatment results "does not appear to be either clinically or statistically significant."(5) Robinson et al responded that there was no statistically significant differences between the groups.(6)
5 March, 2009 - In a rapid response section in the British Medical Journal, Leo and Lacasse raised their concerns about the interpretation of the results of the 2008 trial, and also stated that "during a subsequent internet search we were surprised to learn that four years previously the lead author had been listed on the speaker's bureau for Forest. The omission, however innocent or mistaken, is disturbing; neither the JAMA article nor subsequent media accounts noted that the lead author had served on the speaker's bureau for the manufacturer of Lexapro."(7) Their citation was to our reference 2.
11 March, 2009 - In a letter to JAMA, Robinson and Arndt reported that the financial disclosure for their 2008 article was incomplete, "resulting from erroneous recollection of the appropriate dates for speaking presentations sponsored by pharmaceutical companies...."(8) Dr Robinson disclosed receiving honoraria for two presentations in 2004, and serving on the Forest Laboratories speakers bureau "in 2004 and perhaps 2005." No editorial comment accompanied this letter.
So far, this seems to be a familiar story about an author who seemed to be excessively enthusiastic about a product of the company with whom he had had a financial relationship, but reluctant to disclose this relationship. But wait,
20 March, 2009 - A rather extraordinary editorial was published electronically in JAMA on 20 March, 2009.(9) Let me review its main points, section by section.
After acknowledging the attention conflicts of interest now receive, and briefly describing the 2008 study and the subsequent letter by Lacasse and Leo, the editorial stated that JAMA editors had received a communication from Leo on or after 16 October, 2008 which "indicated he had evidence that Robinson had not reported in his article that he had served on the speakers bureaus for pharmaceutical companies."
The editorial then devoted several paragraphs explaining the "due diligence" JAMA editors used to investigate this "allegation." They noted the "sensitive nature of these investigations," which required them to conduct them "confidentially," and again insisted "these investigations into undisclosed conflicts of interest are time-intensive and require careful attention." Thus, from the time Leo sent his "allegations," (apparently 16 October, 2008), it took until 31 January, 2009 to get a letter from Robinson et al acknowledging his undisclosed conflicts, and until 11 March, 2009 to publish it, a total of five months.
However, the concerns with confidentiality, and the repeated emphasis on the need for unusually painstaking investigation seemed disconnected to the particular case. It is clear that it may take quite a bit of time and effort to investigate some allegations of undisclosed conflicts of interest, especially when the allegations are vague, but the alleged conflicts are severe. However, in this case, it should have taken trivial effort to find Dr Robinson's previous, published disclosures. (It took me about 5 minutes of internet searching to find the two 2005 articles.) Once (easily) discovered, the disclosures in the 2005 articles starkly contrast with the disclosures, or lack thereof in the 2008 article. Furthermore, since these disclosures were already in the public domain, there should have been no concerns with confidentiality.
Nonetheless, the editors then asserted:
This makes no sense. There was no need for confidentiality, because the allegations were not based on whistle-blowing or confidential information. They were based on published articles, articles which clearly disclosed Dr Robinson's financial ties to Forest Laboratories. Anyone who bothered to do a simple Google search could have found that Dr Robinson's disclosure in his 2008 JAMA article did not agree with his disclosure in several 2005 articles. Lacasse and Leo used no confidential information whatsoever in making their allegations. Actually, they were not making "allegations," but simply pointing out that an author had published statements which were inconsistent. Since Lacasse and Leo were simply pointing discrepancies among published articles, how could they have breached "confidentiality," ethically or not?
Second, there was no need for a complex or prolonged investigation. The discrepancies were apparent as soon as one viewed the published articles side by side.
The third point was a non sequitur, and a classic example of blaming the messenger for the message. JAMA had published an article. Other journals published other articles. Publishing these articles put them in the public domain. If comparison of these articles in the public domain were to reflect badly on on of their publishers, it would not be the fault of making the comparison.
Regardless of the illogical nature of their concerns with non-existent confidentiality, assertions that it takes a long, complex investigation to demonstrate the obvious, and their aspersions on the messenger for the message, the JAMA editors then revealed that:
Furthermore, the editors proposed punishing Leo, first by effectively banning him from publishing in the pages of JAMA,
Then, by complaining to his supervisor
Finally, they seemed bitterly offended that the British Medical Journal would publish anything that disagreed with anything printed in JAMA:
Again, rather than raising unsubstantiated allegations, Leo and Lacasse's letter to the BMJ simply showed the discrepancy between the disclosures in Robinson and colleagues' 2008 JAMA article and those in one of his 2005 articles. Both articles are publicly available. What useful information about the letter above and beyond that provided by viewing the discrepant articles could the JAMA editors have provided?
While the JAMA editors castigated Leo for unethical behavior, and sought to punish him for it, they said nothing negative about Robinson. Yet it was Dr Robinson who was supposed to disclose his conflicts to JAMA, but who managed to forget conflicts that he had disclosed before. Why would would it be more unethical to point out publicly available evidence about failure to disclose conflicts of interest than to conceal these conflicts in the first place?
This story is saddening. JAMA has published many important and useful articles on conflicts of interest, and other matters relevant to Health Care Renewal. We have probably favorably cited more editorials by JAMA on these topics than those in any other journal. Yet now the journal's leadership seems to have somehow lost their way. Instead of trying to constructively respond to criticism, they now seem intent on punishing the critics. I hope they find their compass soon, before an important medical institution really is irreparably damaged.
Note: another detailed analysis of this case is here in the Hooked: Ethics, Medicine and Pharma blog. Here is Professor Leo's response to the JAMA ediorial.
ADDENDUM (24 March, 2009) - see also the extensive analysis of this case on the Respectful Insolence blog, and the comments here on the Effect Measure blog, here on Gooznews, and here on KevinMD.
References
1. Evans DL, Charney DS, Lewis L et al. Mood disorders in the medically ill: scientific review and recommendations. Biol Psychiatry 2005; 58: 175-189. [Link here.]
2. Robinson RG, Zorowitz RD. Pseudobulbar affect and stroke. Stroke: Clinical Updates 2005; XV (Jan-Feb). [Link here.]
3. Robinson RG, Jorge RE, Moser DJ et al. Escitalopram and problem-solving therapy for prevention of poststroke depression: a randomized controlled trial. JAMA 2008; 299: 2391-2400. [Link here.]
4. Elias M. Study: antidpressants help stroke victims. USA Today, May 27, 2008.
5. Lacasse J, Leo J. Escitalopram, problem-solving therapy, and poststroke depression. JAMA 2008; 300: 1757-1758.
6. Robinson RG, Jorge RE, Arndt S. Escitalopram, problem-solving therapy, and poststroke depression. JAMA 2008; 300: 1758-1759.
7. Leo J, Lacasse J. Clinical trials of therapy versus medication: even in a tie, medication wins. Brit Med J, 2009: 338: b464. [Link here.]
8. Robinson RG, Arnd S. Incomplete financial disclosure in a study of escitalopram and problem-solving therapy for prevention of poststroke depression. JAMA 2009; 301: 1023-1024. [Link here.]
9. DeAngelis CD, Fontanarosa PB. Conflicts over conflicts of interest. JAMA 2009; 301: [Link here.]
2005 - In a multi-author review article on mood disorders in the medically ill, Dr Robert G Robinson, of the University of Iowa, disclosed that he served on the speakers bureau of Forest Laboratories.(1) In an article in Stroke: Clinical Updates, he made a similar disclosure.(2)
28 May, 2008 - Dr Robinson was the first author of an article published in JAMA that described a randomized controlled trial comparing placebo, problem-solving (cognitive talking) therapy, and escitalopram (Lexapro, Forest Laboratories) in the prevention of depression in patients who have had strokes.(3) Patients who received placebo had a higher rate of depression (11 major, 2 minor cases, 22.4%) than patients who received escitalopram (3, 2, 8.5%) or who received problem-solving therapy (5,2, 11.9%). At the end of the article, Dr Robinson disclosed, "over the past 5 years, Dr Robinson reports serving as a consultant to the former Hamilton Pharmaceutical Company and Avanir Pharmaceutical Company," but made no disclosure about any financial relationship with Forest. In a news article published the day before, Dr Robinson was quoted as saying, "I think every stroke patient who can tolerate an antidepressant should be given one to prevent depression," but did not advocate the use of problem solving therapy.(4)
15 October, 2008 - In a letter to JAMA, Lacasse and Leo asked whether Robinson et al had done an analysis directly comparing problem-solving therapy and escitalopram, and noted that the reported incidence data for stroke in the two treatment groups suggest that the difference in treatment results "does not appear to be either clinically or statistically significant."(5) Robinson et al responded that there was no statistically significant differences between the groups.(6)
5 March, 2009 - In a rapid response section in the British Medical Journal, Leo and Lacasse raised their concerns about the interpretation of the results of the 2008 trial, and also stated that "during a subsequent internet search we were surprised to learn that four years previously the lead author had been listed on the speaker's bureau for Forest. The omission, however innocent or mistaken, is disturbing; neither the JAMA article nor subsequent media accounts noted that the lead author had served on the speaker's bureau for the manufacturer of Lexapro."(7) Their citation was to our reference 2.
11 March, 2009 - In a letter to JAMA, Robinson and Arndt reported that the financial disclosure for their 2008 article was incomplete, "resulting from erroneous recollection of the appropriate dates for speaking presentations sponsored by pharmaceutical companies...."(8) Dr Robinson disclosed receiving honoraria for two presentations in 2004, and serving on the Forest Laboratories speakers bureau "in 2004 and perhaps 2005." No editorial comment accompanied this letter.
So far, this seems to be a familiar story about an author who seemed to be excessively enthusiastic about a product of the company with whom he had had a financial relationship, but reluctant to disclose this relationship. But wait,
20 March, 2009 - A rather extraordinary editorial was published electronically in JAMA on 20 March, 2009.(9) Let me review its main points, section by section.
After acknowledging the attention conflicts of interest now receive, and briefly describing the 2008 study and the subsequent letter by Lacasse and Leo, the editorial stated that JAMA editors had received a communication from Leo on or after 16 October, 2008 which "indicated he had evidence that Robinson had not reported in his article that he had served on the speakers bureaus for pharmaceutical companies."
The editorial then devoted several paragraphs explaining the "due diligence" JAMA editors used to investigate this "allegation." They noted the "sensitive nature of these investigations," which required them to conduct them "confidentially," and again insisted "these investigations into undisclosed conflicts of interest are time-intensive and require careful attention." Thus, from the time Leo sent his "allegations," (apparently 16 October, 2008), it took until 31 January, 2009 to get a letter from Robinson et al acknowledging his undisclosed conflicts, and until 11 March, 2009 to publish it, a total of five months.
However, the concerns with confidentiality, and the repeated emphasis on the need for unusually painstaking investigation seemed disconnected to the particular case. It is clear that it may take quite a bit of time and effort to investigate some allegations of undisclosed conflicts of interest, especially when the allegations are vague, but the alleged conflicts are severe. However, in this case, it should have taken trivial effort to find Dr Robinson's previous, published disclosures. (It took me about 5 minutes of internet searching to find the two 2005 articles.) Once (easily) discovered, the disclosures in the 2005 articles starkly contrast with the disclosures, or lack thereof in the 2008 article. Furthermore, since these disclosures were already in the public domain, there should have been no concerns with confidentiality.
Nonetheless, the editors then asserted:
While the confidential investigation of unreported conflicts of interest is under way, we consider involvement of third parties— such as Leo had done by his posting on the BMJ site and by contacting the media—to be a serious ethical breach of confidentiality that not only potentially damages our ability to complete a fair and thorough investigation (of the specific issue that Leo had brought to our attention), but also potentially damages JAMA’s reputation by the insinuation that we would fail to do so.
This makes no sense. There was no need for confidentiality, because the allegations were not based on whistle-blowing or confidential information. They were based on published articles, articles which clearly disclosed Dr Robinson's financial ties to Forest Laboratories. Anyone who bothered to do a simple Google search could have found that Dr Robinson's disclosure in his 2008 JAMA article did not agree with his disclosure in several 2005 articles. Lacasse and Leo used no confidential information whatsoever in making their allegations. Actually, they were not making "allegations," but simply pointing out that an author had published statements which were inconsistent. Since Lacasse and Leo were simply pointing discrepancies among published articles, how could they have breached "confidentiality," ethically or not?
Second, there was no need for a complex or prolonged investigation. The discrepancies were apparent as soon as one viewed the published articles side by side.
The third point was a non sequitur, and a classic example of blaming the messenger for the message. JAMA had published an article. Other journals published other articles. Publishing these articles put them in the public domain. If comparison of these articles in the public domain were to reflect badly on on of their publishers, it would not be the fault of making the comparison.
Regardless of the illogical nature of their concerns with non-existent confidentiality, assertions that it takes a long, complex investigation to demonstrate the obvious, and their aspersions on the messenger for the message, the JAMA editors then revealed that:
A telephone conversation intended to inform Leo that his actions were inappropriate transformed into an argumentative discussion, as Leo continued to refuse to acknowledge any problems with his actions, even after he was informed that the investigation was completed and was advised to read the upcoming March 11 issue of JAMA (where the letter of explanation and apology from Robinson and the formal correction were in press).
Furthermore, the editors proposed punishing Leo, first by effectively banning him from publishing in the pages of JAMA,
Leo also was informed that, if his actions represented his apparent lack of confidence in and regard for JAMA, he certainly should not plan to submit future
manuscripts or letters for publication.
Then, by complaining to his supervisor
However, since Leo apparently did not appreciate the serious implications of his actions, despite our attempts to explain, we felt an obligation to notify the dean of his institution about our concerns of how Leo’s actions were potentially damaging to JAMA’s reputation. We sought the dean’s assistance in resolving this issue involving a member of the faculty of his institution, to assure there would be no need to publicly identify that faculty member. No dean wants his or her institution implicated in a publication reflecting improper behavior by a faculty member.
Finally, they seemed bitterly offended that the British Medical Journal would publish anything that disagreed with anything printed in JAMA:
In addition, we were dismayed that BMJ would post the article by Leo with the allegations against Robinson and the negative insinuations about JAMA, without at least contacting JAMA to verify the veracity of the report.
Again, rather than raising unsubstantiated allegations, Leo and Lacasse's letter to the BMJ simply showed the discrepancy between the disclosures in Robinson and colleagues' 2008 JAMA article and those in one of his 2005 articles. Both articles are publicly available. What useful information about the letter above and beyond that provided by viewing the discrepant articles could the JAMA editors have provided?
While the JAMA editors castigated Leo for unethical behavior, and sought to punish him for it, they said nothing negative about Robinson. Yet it was Dr Robinson who was supposed to disclose his conflicts to JAMA, but who managed to forget conflicts that he had disclosed before. Why would would it be more unethical to point out publicly available evidence about failure to disclose conflicts of interest than to conceal these conflicts in the first place?
This story is saddening. JAMA has published many important and useful articles on conflicts of interest, and other matters relevant to Health Care Renewal. We have probably favorably cited more editorials by JAMA on these topics than those in any other journal. Yet now the journal's leadership seems to have somehow lost their way. Instead of trying to constructively respond to criticism, they now seem intent on punishing the critics. I hope they find their compass soon, before an important medical institution really is irreparably damaged.
Note: another detailed analysis of this case is here in the Hooked: Ethics, Medicine and Pharma blog. Here is Professor Leo's response to the JAMA ediorial.
ADDENDUM (24 March, 2009) - see also the extensive analysis of this case on the Respectful Insolence blog, and the comments here on the Effect Measure blog, here on Gooznews, and here on KevinMD.
References
1. Evans DL, Charney DS, Lewis L et al. Mood disorders in the medically ill: scientific review and recommendations. Biol Psychiatry 2005; 58: 175-189. [Link here.]
2. Robinson RG, Zorowitz RD. Pseudobulbar affect and stroke. Stroke: Clinical Updates 2005; XV (Jan-Feb). [Link here.]
3. Robinson RG, Jorge RE, Moser DJ et al. Escitalopram and problem-solving therapy for prevention of poststroke depression: a randomized controlled trial. JAMA 2008; 299: 2391-2400. [Link here.]
4. Elias M. Study: antidpressants help stroke victims. USA Today, May 27, 2008.
5. Lacasse J, Leo J. Escitalopram, problem-solving therapy, and poststroke depression. JAMA 2008; 300: 1757-1758.
6. Robinson RG, Jorge RE, Arndt S. Escitalopram, problem-solving therapy, and poststroke depression. JAMA 2008; 300: 1758-1759.
7. Leo J, Lacasse J. Clinical trials of therapy versus medication: even in a tie, medication wins. Brit Med J, 2009: 338: b464. [Link here.]
8. Robinson RG, Arnd S. Incomplete financial disclosure in a study of escitalopram and problem-solving therapy for prevention of poststroke depression. JAMA 2009; 301: 1023-1024. [Link here.]
9. DeAngelis CD, Fontanarosa PB. Conflicts over conflicts of interest. JAMA 2009; 301: [Link here.]
Integrated Nutrition, Lifestyle and Health Database
Ricardo from the website Canibais e Reis has just released a fantastic resource for anyone who's interested in the relationship between nutrition, lifestyle and health. It's an excel spreadsheet that integrates information from several international sources, including:
You can read more about the database and download it here.
- UN Food and Agriculture Organization Statistical Yearbook
- FAOSTAT food consumption database
- British Heart Foundation Health Statistics database
- World Health Organization Global Health Atlas
You can read more about the database and download it here.
Integrated Nutrition, Lifestyle and Health Database
Ricardo from the website Canibais e Reis has just released a fantastic resource for anyone who's interested in the relationship between nutrition, lifestyle and health. It's an excel spreadsheet that integrates information from several international sources, including:
You can read more about the database and download it here.
- UN Food and Agriculture Organization Statistical Yearbook
- FAOSTAT food consumption database
- British Heart Foundation Health Statistics database
- World Health Organization Global Health Atlas
You can read more about the database and download it here.
Subscribe to:
Posts (Atom)